EFFECT OF ACAMPROSATE IN EXPERIMENTAL MODELS OF PERIPHERAL NEUROPATHIC AND INFLAMMATORY PAIN IN WISTAR RATS

Neuropathic pain is a persistent chronic pain caused by primary lesion or dysfunction of neurons which is primarily characterized by hyperalgesia, allodynia. There is some evidence that acamprosate might inhibit Ca2 influx through NMDA and voltage-dependent Ca2 channels. λ-carrageenan (0.1 ml of 1% w/v) into i.pl. region of the hind paw was injected to produce acute inflammation. Unilateral peripheral mononeuropathy was induced by sciatic nerve ligation. Thermal and mechanical hyperalgesia and cold allodynia were assessed. The extent of oxido-nitrosative stress was assessed by estimating the levels of thiobarbituric acid reactive substances, catalase and superoxide dismutase activity and nitrite levels in both sciatic nerve and dorso-lumbar spinal cord homogenate in CCI model. The one hour pre-treatment with acamprosate (100 and 200 mg/kg, p.o) was given. Then second dose acamprosate treatment at the 19 hr post-carrageenan given after first dose oral administration of acamprosate at a dose of 200 mg/kg., but not 100 mg/kg significantly reversed the established mechanical hyperalgesia without producing significant effect on thermal hyperalgesia. The two week repeated administration of acamprosate (100 and 200 mg/kg, p.o.) significantly reversed the established thermal and mechanical hyperalgesia and cold allodynia. Thus, single dose treatment with acamprosate did not produce significant anti-inflammatory and anti-hyperalgesic effects, in carrageenan-induced inflammatory pain model. While, repeated administration of acamprosate ameliorates the behavioural symptoms of neuropathic pain observed CCI-induced NP. The observed effects may be partly due to activation of anti-oxidant mechanisms, but independent of anti-inflammatory effects